Influence of Substituent Chain Branching on the Transfection Efficacy of Cyclopropenium-Based Polymers.
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ABSTRACT:
SUBMITTER: Brucks SD
PROVIDER: S-EPMC6431972 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:"Side chain engineering" research has yielded many promising and beneficial results, with applications in various fields. However, this research did not receive sufficient focus when nature-sourced polymers are concerned. In this study, we have performed side chain engineering on chitosan, a nature-sourced polysaccharide, by coupling it with a number of aliphatic aldehydes of varying chain lengths. The side chains' length and the pursuing effect on the modified products' properties were studied in great detail. In terms of coupling yields, it was found that some substituents have displayed more favorable results than others by a factor of over 35 times. When studying the modified polymers' physical and mechanical properties, some of them were found to exhibit more rigid mechanical properties by a factor of 3.5 times than others. The effect was also expressed through self-assembly concentrations and encapsulation capabilities of the modified polymers. Remarkably, the combined experimental and calculated kinetic studies showed the results do not necessarily follow a linear progression relating to substituent chain length, but rather a parabolic pattern with a specific extremum point. This study has assisted in shedding light on the inspected phenomenon, explaining that not only steric and electronic factors but also interfacial solubility related factors govern the coupling reaction and the resulting modified polymers' properties. As chemical protocols in various academic, clinical, and industrial studies around the world slowly shift their norms toward finding safer ways for the production of novel materials and technologies, nature-sourced polymers hold great promise as virtually inexhaustible raw materials. The perfection of their chemical modification is therefore relevant now more than ever, with far-reaching and diverse applicative prospects.
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Project description:BackgroundFormulation of DNA/cationic lipid complexes (lipoplexes) designed for nucleic acid delivery mostly results in positively charged particles which are thought to enter cells by endocytosis. We recently developed a lipoplex formulation called Neutraplex that allows preparation of both cationic and anionic stable complexes with similar lipid content and ultrastructure.Methodology/principal findingsTo assess whether the global net charge could influence cell uptake and activity of the transported oligonucleotides (on), we prepared lipoplexes with positive and negative charges and compared: (i) their physicochemical properties by zeta potential analysis and dynamic light scattering, (ii) their cell uptake by fluorescence microscopy and flow cytometry, and (iii) the biological activity of the transported ON using a splicing correction assay. We show that positively or negatively charged lipoplexes enter cells cells using both temperature-dependent and -independent uptake mechanisms. Specifically, positively charged lipoplexes predominantly use a temperature-dependent transport when cells are incubated OptiMEM medium. Anionic lipoplexes favour an energy-independent transport and show higher ON activity than cationic lipoplexes in presence of serum. However, lipoplexes with high positive global net charge and OptiMEM medium give the highest uptake and ON activity levels.ConclusionsThese findings suggest that, in addition to endocytosis, lipoplexes may enter cell via a temperature-independent mechanism, which could be mediated by lipid mixing. Such characteristics might arise from the specific lipoplex ultrastructure and should be taken into consideration when developing lipoplexes designed for in vivo or ex vivo nucleic acid transfer.
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